RT Journal Article
SR Electronic
T1 Antibody Multispecificity Mediated by Conformational Diversity
JF Science
JO Science
FD American Association for the Advancement of Science
SP 1362
OP 1367
DO 10.1126/science.1079731
VO 299
IS 5611
A1 James, Leo C.
A1 Roversi, Pietro
A1 Tawfik, Dan S.
YR 2003
UL http://science.sciencemag.org/content/299/5611/1362.abstract
AB A single antibody was shown to adopt different binding-site conformations and thereby bind unrelated antigens. Analysis by both x-ray crystallography and pre–steady-state kinetics revealed an equilibrium between different preexisting isomers, one of which possessed a promiscuous, low-affinity binding site for aromatic ligands, including the immunizing hapten. A subsequent induced-fit isomerization led to high-affinity complexes with a deep and narrow binding site. A protein antigen identified by repertoire selection made use of an unrelated antibody isomer with a wide, shallow binding site. Conformational diversity, whereby one sequence adopts multiple structures and multiple functions, can increase the effective size of the antibody repertoire but may also lead to autoimmunity and allergy.